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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 892-899 
    ISSN: 1420-9071
    Schlagwort(e): Adjuvant arthritis ; experimental allergic uveitis ; periarteritis nodosa ; diabetes mellitus ; prolactin ; bromocryptine ; cyclosporine A
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 52 (1996), S. 900-908 
    ISSN: 1420-9071
    Schlagwort(e): Freund's complete adjuvant ; diurnal rhythms ; ornithine decarboxylase ; prolactin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0584
    Schlagwort(e): Key words CD4+ T lymphocytes ; CD45 isoforms ; Interleukin-1β ; Luteinizing hormone ; Prolactin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The expected association between age and the CD45 isoforms expression on CD4+ T-PBL is much more obvious in men than in women. We investigated whether or not circulating factors influence the differentiation of CD4+ T-PBL. Peripheral blood samples were obtained from 56 healthy age-matched subjects (28 men and 28 women, 21–55 years old). Mononuclear leukocytes were analyzed by three-color flow cytometry. The serum concentrations of interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α (TNF-α), GM colony-stimulating factor, prolactin (Prl), and luteinizing hormone (LH) were determined by ELISA. The expected age-related decrease of naive (CD45RA+,RO–) cells and increase of memory (CD45RA–,RO+) cells among CD4+ T-PBL were observed in men only (p〈0.001 and 0.005). In women, these correlations were not significant. On the other hand, in women only, elevated IL-1β was associated with fewer naive and more memory cells among CD4+ T-PBL (p〈0.001). In both sexes, IL-1β correlated with the expression of CD25 on CD4+ T-PBL (on either naive or memory cells, p〈0.001). Other cytokines or the CD8+ T-PBL showed no significant correlation. In women, the elevation of LH at mid-cycle inversely correlated with the proportion of naive CD4+ T-PBL (p〈0.01). Elevated LH was associated with more CD25 on memory CD4+ T-PBL (p〈0.01). A significant correlation exists between IL-1β and LH (p〈0.001). Furthermore, in both sexes, Prl correlated with the proportion of CD4+ cells among T-PBL. In men, elevated Prl was associated with more naive CD4+ T-PBL (p〈0.005), while in women, Prl correlated with more transient CD45RA+, RO+ cells among CD4+ T-PBL and increased TNF-α (p〈0.05 for both). Thus, circulating IL-1β could be involved in the expression of CD25 on CD4+ T-PBL and favors the generation of memory CD4+ T-PBL. In women, the IL-1β- and/or mid-cycle-dependent processes seem to overwhelm the age-related changes. Elevated Prl might exert a dual influence: it favors the development of naive CD4+ T lymphocytes and possibly acts in, synergy with other cytokines during immune stimulation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1437-160X
    Schlagwort(e): Rheumatoid arthritis ; Peripheral blood T-lymphocytes ; CD45 isoforms ; IgM rheumatoid factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated whether, in rheumatoid arthritis (RA), the CD45 isoform expression of peripheral blood T-lymphocytes (T-PBL) is related to auto-immune processes (e.g. IgM rheumatoid factors) and to clinical manifestations. By three-colour flow cytometry, we quantified three subsets of CD4+ or CD8+ T-PBL: “naive” CD45RA+,RO−, “transient” CD45RA+,RO+, and “memory” CD45RA−,RO+ cells, in 102 patients with RA and in 41 age- and sex-matched controls. The serum levels of rheumatoid factors (RF) were determined — besides conventional agglutination tests — by ELISA (IgM-RF). Extensive clinical examination was performed at the time of blood sampling. In RA, age, sex and drug therapy did not constitute major influences on the CD45RA/RO patterns. In “healthy” men, higher age significantly correlated with fewer naive and more memory CD4+ T-PBL (P〈0.01). In RA, distinct correlations between the T-PBL subsets, autoimmune and clinical manifestations became obvious when patients with low and high levels of RF against human IgG Fc fragments, as determined by ELISA, were analysed separately. RA patients with high IgM-RF had elevated proportions of CD45RO+ T-PBL (P〈0.05), that correlated with clinical parameters of disease activity (tender joint count, Ritchie index, P〈0.05) and outcome (Health Assessment Questionnaire, Larsen radiographic scores, P〈0.05). The proportions of memory CD4+ and CD8+ T-PBL correlated strongly (P〈0.001) with the IgM-RF levels. Within 1 year, only three of 34 patients (disease duration of 5–9 years) showed seroconversion from low to high levels of IgM-RF (and positive agglutination tests); this was paralleled by reductions in naive and increases in transient T-PBL (P〈0.02). Thus, in RA, the proportions of memory CD4+ and CD8+ T-PBL correlate with the level of IgM-RF and, together with transient T-PBL, with clinical parameters of disease activity and outcome.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1437-160X
    Schlagwort(e): Rheumatoid arthritis ; Peripheral blood T-lymphocytes ; CD45 isoforms ; CD29
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of this study was to quantify and characterise the CD4+ and CD8+, CD45RA+, CD45RO- T-lymphocytes that paradoxically expressed the CD29 bright+ phenotype in health and in rheumatoid arthritis. We further evaluated their clinical implications. Blood samples were obtained from 100 patients with rheumatoid arthritis and 40 age- and sex-matched controls. Cell surface antigens and interleukin-2 (IL-2) binding were detected on CD4+ and CD8+ peripheral blood T-lymphocytes (T-PBL) by three-colour flow cytometry. One-third of the patients were clinically evaluated at the time of blood sampling. In healthy donors, we found 16 ± 14% of CD29 bright+cells among CD4+, CD45RA+, RO-T-PBL. These “false naive” CD4+ T-PBL were Leu-8+, and a majority expressed the CD25/p55 receptor (IL-2Rα chain), while a minority showed the CDlla bright+, CD69+ and/or CD 122/p75+ (IL-2Rβ chain) phenotype, and few cells were CD31 bright+ and HLA-DR+. In rheumatoid arthritis, their proportion among CD4+, CD45RA+, RO- cells increased to 25 ± 15% (P 〈 0.001, compared with controls). In patients, the reductions in CD31 and CD38 expression (P 〈 0.05 for both), as well as the enhanced CD25 expression (P 〈 0.001) on CD4+, CD45RA+, RO- T-PBL reflected a more differentiated phenotype. The occurrences of CD25 and CD122 were increased on false naive CD4+ T-PBL (0.01 〈P〈0.001); however, the binding of IL-2 remained very low (in contrast to the binding of IL-2 on CD45RO+ T-PBL). Furthermore, a major subset of CD8+, CD45RA+, RO- T-PBL (45 ± 17% in controls) expressed the CD29 bright+ phenotype. These “false naive” CD8+ T-PBL included a great many of CID 1lb+, CD28- cells, while a minority showed the HLA-DR+, CD69+ and/orCD122+ phenotypes. Patients with low levels of IgM rheumatoid factors (IgM-RF; but with active disease) had an elevated proportion of CD45RA+, RO-cells among the CD8+ T-PBL, in part due to an increased proportion of false naive cells (P 〈 0.05). In patients, the false naive CD8+ T-PBL showed down-regulated CD1lb and an increased expression of IL-2 receptor chains (CD25 and CD 122; 0.05 〈P 〈 0.01), but without a significant increase in IL-2 binding. More CD69 on false naive CD8+ T-PBL was found in patients with high levels of IgM-RF (P 〈 0.005 compared to patients with low 19M-RF). Finally, both false naive CD4+ and CD8+ T-PBL correlated with the clinical process and outcome variables (0.05 〈P 〈0.01). The levels of activated false naive CD4+ T-PBL (CD25+ and/or CD122+) or CD8+ T-PBL (CD69+ and/or CD122+) were associated with clinical parameters of disease activity (0.05 〈P 〈 0.01). Thus, in rheumatoid arthritis, false naive T-PBL showed important qualitative differences. The levels of activated false naive T-PBL could be particularly interesting for monitoring disease evolution.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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